Steroid-induced ocular hypertensive response in pediatric patients with acute lymphoblastic leukemia.

PURPOSE: To report the characteristics of the steroid-induced ocular hypertensive response in pediatric patients with acute lymphoblastic leukemia (ALL) treated with prednisolone (PSL) during induction therapy and with dexamethasone (DEX) during reinduction therapy. STUDY DESIGN: Retrospective. PATIENTS AND METHODS: This study included pediatric patients diagnosed with B-cell precursor ALL and treated with systemic corticosteroids sometime during the period from 2016 to 2018 at Shizuoka Children's Hospital. Data were extracted from the hematology/oncology records related to the type, dose, and duration of systemic corticosteroids as well as to the ophthalmologic examination findings, intraocular pressure (IOP) data, symptoms of high IOP, and antiglaucoma medications obtained during corticosteroid administration. The maximal IOPs of the PSL and DEX groups were compared. RESULTS: Twenty-eight patients (18 boys and 10 girls; mean age 5.5 years) were treated with systemic corticosteroids. Twelve of the 22 courses of PSL and 33 of the 44 courses of DEX were found to be associated with high IOP. The maximal IOP was higher with the use of DEX than with the use of PSL, including in those who received prophylactic therapy (PSL 25.2 mmHg, DEX 33.6 mmHg; P = 0.02). Antiglaucoma medication was given to 21 patients; 6 patients had symptoms of ocular hypertension. The maximal IOPs were 52.8 mmHg and 70.8 mmHg in the PSL and DEX groups, respectively. Both groups of patients reported severe headache. CONCLUSION: Increased IOP was frequently observed during systemic corticosteroid therapy in pediatric patients with ALL. Although most patients were asymptomatic, they occasionally presented with severe systemic symptoms. Regular ophthalmologic examinations should be included in the treatment guidelines for ALL.

Evaluation of Surgical Strategy Based on the Intraoperative Superior Oblique Tendon Traction Test.

PURPOSE: To clarify the efficacy of a surgical strategy based on the superior oblique tendon traction test. METHODS: A retrospective chart review was performed between January 2002 and June 2015. During that period, a single inferior oblique muscle (IO) myectomy and a combined IO myectomy and superior oblique muscle (SO) tuck procedure were performed based on SO tendon looseness as revealed by a traction test. The surgical effects of both procedures and the number of operations were analyzed. RESULTS: Sixty-five cases were retrieved. Seventy-four surgeries were required. The IO myectomy and simultaneous groups included 48 and 17 cases, respectively. Pre-operative vertical deviation was significantly lower in the IO myectomy (11.8 prism diopters) than in the simultaneous (27.2 prism diopters; Mann-Whitney U-test, P < 0.001) group. The mean induced changes were 9.4 prism diopters and 21.6 prism diopters in the IO myectomy and simultaneous groups, respectively, and the postoperative vertical deviation was not significantly different. On average, 1.13 and 1.18 surgeries per patient were performed in the IO myectomy and simultaneous groups, respectively. CONCLUSION: The simultaneous surgery of inferior oblique myectomy and superior oblique tuck is safe and effective for treating large angle of congenital/idiopathic superior oblique palsy with a lax superior oblique tendon, as determined by the traction test.

Phospholipase C δ1 in macrophages negatively regulates TLR4-induced proinflammatory cytokine production and Fcγ receptor-mediated phagocytosis.

Macrophages are key players in the innate immune response. Turnover of phosphoinositides (PI), particularly phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2), has been implicated in macrophage functions such as toll-like receptor (TLR)-mediated cytokine production and phagocytosis. However, PI metabolizing enzymes responsible for macrophage functions are not well defined. The phospholipase C (PLC) family of enzymes is critical in PI(4,5)P2 turnover. In this study, we investigated the role of PLCδ1, a prototype PLC, in macrophages on the expression of inflammation-associated genes and phagocytosis. Lipopolysaccharides (LPS) signal through TLR4 to produce proinflammatory cytokines such as interleukin (IL)-1ß. LPS stimulation of both RAW264.7 murine macrophages and murine bone marrow-derived macrophages resulted in lower PLCδ1 mRNA and protein expression levels, compared to that in the control. Using chemical inhibitor compounds, we demonstrated that the up-regulation of p38 MAPK activity led to down-regulation of PLCδ1 mRNA expression in macrophages. PLCδ1 reduction by RNAi or gene deletion resulted in greater LPS-induced IL-1ß expression than that observed in the control siRNA-treated cells, without increasing TLR4 cell surface expression. PLCδ1 also negatively regulated LPS-induced cell spreading. Analysis of Fcγ receptor-mediated phagocytosis demonstrated an increased phagocytosis index after PLCδ1 knockdown in RAW264.7 cells. Conversely, overexpression of PLCδ1 reduced phagocytosis whereas catalytic inactive PLCδ1 had no effect. Altered levels of PLCδ1 affected the binding of opsonized latex beads with cells, rather than the phagocytic activity. Taken together, the data suggest that PLCδ1 negatively regulates LPS-induced production of IL-1ß and Fcγ receptor-mediated phagocytosis in macrophages.

Characteristics and surgical outcomes of consecutive exotropia of different etiologies.

PURPOSE: To investigate the surgical results for consecutive exotropia with or without insertion abnormalities on the basis of the position of the lateral rectus muscle at surgery. METHODS: Patients with consecutive exotropia who had undergone medial rectus recession as a primary procedure or advancement of previously recessed medial rectus muscles from 2002 to 2012 were included in the study. The characteristics, postoperative courses, and final results were compared among 3 patient groups. The patients' characteristics including sex, refractive error, and age at the initial surgery were compared. The main outcome measures were the angles of deviation in the primary position and the average divergent drift per month after the exotropia surgery. RESULTS: Twenty-four eyes of 23 patients were investigated. The patients were divided into 3 groups according to insertion status: with normal muscle insertion (4 men, 4 women), slipped muscles (9 women), and stretched scars (2 men, 4 women). The preoperative angles of deviation at near differed significantly between the slipped muscle group and the normal muscle insertion group (P = 0.02). Only patients with normal insertions had significantly greater hyperopia in the nondominant eye (0.95 D) than in the dominant eye (0.53 D). The postoperative divergent shift per month was similar among the groups (0.3, 0.1, and 0.2 prism diopters per month in the slipped muscle, stretched scar, and normal muscle insertion groups, respectively; P = 0.70). CONCLUSIONS: Hyperopic anisometropia is an important factor in the natural course of outward drift. The postoperative course of advancement of the medial rectus muscle was equally stable in all 3 patient groups.

A case of aniridia with unilateral Peters anomaly.

Aniridia is an autosomal-dominant, panocular, congenital anomaly transmitted with high penetrance and largely caused by mutations in the PAX6 gene. Although Peters anomaly may also be caused by mutations in PAX6, there has not to our knowledge been a report of aniridia associated with lens displacement into the anterior chamber and lenticular-corneal attachment. We report a child with aniridia and Peters anomaly associated with a PAX6 gene mutation.

Magnetic resonance imaging of the medial rectus muscle of patients with consecutive exotropia after medial rectus muscle recession.

PURPOSE: To investigate the morphologic characteristics of the medial rectus muscle in patients with consecutive exotropia. DESIGN: Retrospective, nonrandomized, interventional study. PARTICIPANTS AND CONTROLS: Eleven eyes of 10 patients with consecutive exotropia were studied. Thirteen eyes of 13 age-matched normal subjects were studied as controls. METHODS: All of the patients underwent an advancement of a previously operated medial rectus muscle. Patients were divided into 3 groups based on the insertion of the medial rectus muscle: Normally recessed stretched scar, and slipped muscle. MAIN OUTCOME MEASURES: A comparison was made of the clinical findings, intraoperative findings, and distance from the limbus to the medial rectus muscle measured on magnetic resonance images among the groups. RESULTS: The medial rectus of 4 eyes of 3 patients had normally recessed insertions and 7 eyes had abnormal insertions (3 stretched scars, 4 slipped muscles). The clinical findings were not different among the 3 groups. The magnetic resonance images showed that the medial rectus muscle was located closest to the limbus in the control subjects and most distant in the patients with a slipped muscle (P<0.005). The clinical findings in the patients with a stretched scar and with normally recessed were indistinguishable. CONCLUSIONS: Magnetic resonance images of the medial rectus muscles of the control subjects and operated groups are significantly different morphologically. A slipped medial rectus muscle has characteristic magnetic resonance findings that are distinguishable from the muscle with normally recessed and stretched scar.